A portrait is given of Professor Kelly Chibale, the driving force behind H3D, the drug discovery and development centre at the University of Cape Town, South Africa. He is dedicated to the development of new drugs to fight infectious diseases of poverty that are prevalent in Africa, including MMV390048, the first anti-malarial drug ever to be validated in a Phase I trial in Africa. In 2018 he was recognized as one of Fortune magazine’s top 50 ‘World’s Greatest Leaders’.

Anna K. H. Hirsch, Professor and Head of the Department of Drug Design and Optimisation at the Helmholtz Institute for Pharmaceutical Research in Saarbrücken (HIPS), Germany, is dedicated to fighting infectious diseases by focussing on enzymes that are central to the metabolism of parasites. Her research has led to a valuable collaboration with the Swiss Tropical and Public Health Institute (Swiss TPH).

In pursuing novel therapeutic solutions, drug discovery and development rely on efficiently utilising existing knowledge and resources. Repurposing know-how, a strategy that capitalises on previously acquired information and expertise, has emerged as a powerful approach to accelerate drug discovery and development processes, often at a fraction of the costs of de novo developments. For 80 years, collaborating within a network of partnerships, the Swiss Tropical and Public Health Institute (Swiss TPH) has been working along a value chain from innovation to validation and application to combat poverty-related diseases. This article presents an overview of selected know-how repurposing initiatives conducted at Swiss TPH with a particular emphasis on the exploration of drug development pathways in the context of neglected tropical diseases and other infectious diseases of poverty, such as schistosomiasis, malaria and human African trypanosomiasis.
  

Thanks to its expertise in clinical research, epidemiology, infectious diseases, microbiology, parasitology, public health, translational research and tropical medicine, coupled with deeply rooted partnerships with institutions in low- and middle-income countries (LMICs), the Swiss Tropical and Public Health Institute (Swiss TPH) has been a key contributor in many drug research and development consortia involving academia, pharma and product development partnerships. Our know-how of the maintenance of parasites and their life-cycles in the laboratory, plus our strong ties to research centres and disease control programme managers in LMICs with access to field sites and laboratories, have enabled systems for drug efficacy testing in vitro and in vivo, clinical research, and modelling to support the experimental approaches. Thus, Swiss TPH has made fundamental contributions towards the development of new drugs – and the better use of old drugs – for neglected tropical diseases and infectious diseases of poverty, such as Buruli ulcer, Chagas disease, food-borne trematodiasis (e.g. clonorchiasis, fascioliasis and opisthorchiasis), human African trypanosomiasis, leishmaniasis, malaria, schistosomiasis, soil-transmitted helminthiasis and tuberculosis. In this article, we show case the success stories of molecules to which Swiss TPH has made a substantial contribution regarding their use as anti-infective compounds with the ultimate aim to improve people’s health and well-being.

The year 2023 marks the 80th anniversary of the Swiss Tropical and Public Health Institute (Swiss TPH). Associated with the University of Basel, Swiss TPH combines research, education and services, working across a value chain from innovation and validation to application to improve people’s health and well-being. Around 700 staff and students work in Swiss TPH’s new headquarters in an emerging life-science cluster in Allschwil, Switzerland, focusing on infectious and non-communicable diseases, environment, society and health as well as health systems and interventions. In this special issue of Chimia, we highlight 30 years of research and development (R&D) at Swiss TPH, deeply grounded in partnership, towards new drugs for tropical diseases.

Buruli ulcer (BU) is a chronic necrotizing skin disease caused by Mycobacterium ulcerans. Historically, the disease was treated by surgical excision of the skin lesions, until an 8-week combination therapy of rifampicin and streptomycin was introduced in 2004. This treatment modality was effective and reduced recurrence rates. Rifampicin is the most efficacious antibiotic for the treatment of BU and, should rifampicin-resistant M. ulcerans strains emerge, there is currently no replacement for it. As for mycobacterial diseases in general, there is a pressing need for the development of novel, fast-acting drugs. Under market economy conditions, repurposing of new tuberculosis drug candidates is the most promising avenue for alternative BU treatments. Our drug repurposing activities have led to the identification of several actives against M. ulcerans. In particular, the cytochrome bc1 complex inhibitor telacebec (Q203) is a promising drug candidate for the treatment of BU in Africa and Australia. While an active cytochrome-bd oxidase bypass limits the potency of the cytochrome-bc1-specific inhibitor telacebec against M. tuberculosis, classical lineage M. ulcerans strains rely exclusively on cytochrome-bc1 to respire. Hence, telacebec is effective at nanomolar concentration against M. ulcerans, and a high treatment efficacy in an experimental mouse infection model indicates that treatment of BU could be substantially shortened and simplified by telacebec.

In discussion with Lukas Meier from the Swiss Tropical and Public Health Institute (Swiss TPH), Lutz Hegemann, Head of Novartis Global Health and Sustainability and Marcel Tanner, President of the Swiss Academies of Arts and Sciences, give their opinions on the changes that occurred in drug discovery and development for poverty-related diseases over the past 30 years. They emphasise the power of public–private partnerships and provide their points of views on what needs to be done in the future to ensure that the poorest of the poor also have access to important therapies

The European spruce bark beetles release aggregation pheromones to trigger attack on Norway spruce trees; attracting beetles through the use of pheromone traps proves less effective than conventional forest management.
  
 
  

Quinacrine, the main antimalarial drug during World War II, has had a chequered history that included the successful repurposing as an intrapleural sclerosant for the treatment of malignant pleural effusions, a non-surgical method of female sterilisation, and the use as an immunomodulatory drug in lupus erythematosus. While no longer used for these former indications, quinacrine (re)emerged as an indispensable second-line drug for the treatment of nitroimidazole-refractory Giardia duodenalis infections, and thus depicts an indispensable “orphan drug”.